Structural and dynamical changes of the Streptococcus gordonii metalloregulatory ScaR protein induced by Mn ion binding.

Katarina Radman, Zoe Jelić Matošević, Dijana Žilić, Ivo Crnolatac, Nikola Bregović, Marina Kveder, Ivo Piantanida, Pedro A Fernandes, Ivana Leščić Ašler, Branimir Bertoša

Journal: International journal of biological macromolecules 2023;253(Pt 8):127572

PMID: 37866578

Full Text on Elsevier Science View on PubMed

Abstract

Divalent metal ions are essential micronutrients for many intercellular reactions. Maintaining their homeostasis is necessary for the survival of bacteria. In Streptococcus gordonii, one of the primary colonizers of the tooth surface, the cellular concentration of manganese ions (Mn) is regulated by the manganese-sensing transcriptional factor ScaR which controls the expression of proteins involved in manganese homeostasis. To resolve the molecular mechanism through which the binding of Mn ions increases the binding affinity of ScaR to DNA, a variety of computational (QM and MD) and experimental (ITC, DSC, EMSA, EPR, and CD) methods were applied. The computational results showed that Mn binding induces a conformational change in ScaR that primarily affects the position of the DNA binding domains and, consequently, the DNA binding affinity of the protein. In addition, experimental results revealed a 1:4 binding stoichiometry between ScaR dimer and Mn ions, while the computational results showed that the binding of Mn ions in the primary binding sites is sufficient to induce the observed conformational change of ScaR.

Address: Department of Chemistry, Faculty of Science, University of Zagreb, Horvatovac 102a, 10000 Zagreb, Croatia. Electronic address: [email protected].; Department of Chemistry, Faculty of Science, University of Zagreb, Horvatovac 102a, 10000 Zagreb, Croatia. Electronic address: [email protected].; Division of Physical Chemistry, Ruđer Bošković Institute, 10000 Zagreb, Croatia. Electronic address: [email protected].; Division of Organic Chemistry & Biochemistry, Ruđer Bošković Institute, 10000 Zagreb, Croatia. Electronic address: [email protected].; Department of Chemistry, Faculty of Science, University of Zagreb, Horvatovac 102a, 10000 Zagreb, Croatia. Electronic address: [email protected].; Division of Physical Chemistry, Ruđer Bošković Institute, 10000 Zagreb, Croatia. Electronic address: [email protected].; Division of Organic Chemistry & Biochemistry, Ruđer Bošković Institute, 10000 Zagreb, Croatia. Electronic address: [email protected].; LAQV, REQUIMTE, Department of Chemistry and Biochemistry, Faculty of Science, University of Porto, Rua do Campo Alegre s/n, 4169-007 Porto, Portugal. Electronic address: [email protected].; Division of Physical Chemistry, Ruđer Bošković Institute, 10000 Zagreb, Croatia. Electronic address: [email protected].; Department of Chemistry, Faculty of Science, University of Zagreb, Horvatovac 102a, 10000 Zagreb, Croatia. Electronic address: [email protected].

DOI: 10.1016/j.ijbiomac.2023.127572

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MeSH Terms: Humans, Streptococcus gordonii, Bacterial Proteins, Manganese, Cicatrix, Binding Sites, DNA, Ions, Protein Binding